Revolutionizing breast cancer treatment: Harnessing the related mechanisms and drugs for regulated cell death (Review)

Abstract

Breast cancer arises from the malignant transformation of mammary epithelial cells under the influence of various carcinogenic factors, leading to a gradual increase in its prevalence. This disease has become the leading cause of mortality among female malignancies, posing a significant threat to the health of women. The timely identification of breast cancer remains challenging, often resulting in diagnosis at the advanced stages of the disease. Conventional therapeutic approaches, such as surgical excision, chemotherapy and radiotherapy, exhibit limited efficacy in controlling the progression and metastasis of the disease. Regulated cell death (RCD), a process essential for physiological tissue cell renewal, occurs within the body independently of external influences. In the context of cancer, research on RCD primarily focuses on cuproptosis, ferroptosis and pyroptosis. Mounting evidence suggests a marked association between these specific forms of RCD, and the onset and progression of breast cancer. For example, a cuproptosis vector can effectively bind copper ions to induce cuproptosis in breast cancer cells, thereby hindering their proliferation. Additionally, the expression of ferroptosis‑related genes can enhance the sensitivity of breast cancer cells to chemotherapy. Likewise, pyroptosis‑related proteins not only participate in pyroptosis, but also regulate the tumor microenvironment, ultimately leading to the death of breast cancer cells. The present review discusses the unique regulatory mechanisms of cuproptosis, ferroptosis and pyroptosis in breast cancer, and the mechanisms through which they are affected by conventional cancer drugs. Furthermore, it provides a comprehensive overview of the significance of these forms of RCD in modulating the efficacy of chemotherapy and highlights their shared characteristics. This knowledge may provide novel avenues for both clinical interventions and fundamental research in the context of breast cancer.

Keywords: apoptosis; breast cancer; cuproptosis; ferroptosis; pyroptosis; regulatory cell death.

Figure 1

Comparison of the bidirectional effects of doxorubicin in relation to multiple types of regulated cell death. DOX, doxorubicin; ROS, reactive oxygen species. The figure was prepared using Figdraw.

Figure 2

Comparison of different types of regulated cell death modulating the conventional chemotherapeutic agent, cisplatin. GPX4, glutathione peroxidase 4; GSH, glutathione; GSDMD, gasdermin D. The figure was prepared using Figdraw.

Figure 3

Comparison of the mechanisms of cuproptosis, ferroptosis and cellular pyroptosis. GSH, glutathione; GPX4, glutathione peroxidase 4. The figure was prepared using Figdraw.